Characterisation of gut microbiota of obesity and type 2 diabetes in a rodent model

Abstract

Various studies have suggested that the gut microbiome interacts with the host and may have a significant role in the aetiology of obesity and Type 2 Diabetes (T2D). It was hypothesised that bacterial communities in obesity and T2D differ from control and compromise normal interactions between host and microbiota. Obesity and T2D were developed in rats by feeding a high-fat diet or a high-fat diet plus a single low-dose streptozotocin administration, respectively. The microbiome profiles and their metabolic potentials were established by metagenomic 16S rRNA sequencing and bioinformatics. Taxonomy and predicted metabolism-related genes in obesity and T2D were markedly 2 different from controls and indeed from each other. Diversity was reduced in T2D but not in Obese rats. Factors likely to compromise host intestinal, barrier integrity were found in Obese and T2D rats including predicted, decreased bacterial butyrate production. Capacity to increase energy extraction via ABC-transporters and carbohydrate metabolism were enhanced in Obese and T2D rats. T2D was characterized by increased proinflammatory molecules. While obesity and T2D show distinct differences, results suggest that in both conditions Bacteroides and Blautia species were increased indicating a possible mechanistic link.

Microbiota intestinal en pacientes con Diabetes Mellitus: Análisis de la evidencia actual. Revisión sistemática

“…El acetato es capaz de formar ácidos grasos que luego podrá formar tejido adiposo, triglicéridos y asociarse a lipoproteínas. [26][27][28] Por otro lado, se ha determinado al phylum Firmicutes y a la clase Clostridia dentro de la menos abundantes en este grupo de pacientes, correlacionando Diabetes Mellitus tipo 2 con una baja concentración de este tipo de microorganismos. Algunos estudios describen ratio o diferencias entre Firmicutes/Bacteroidetes evidenciando niveles elevadamente significativos en pacientes con Diabetes Mellitus tipo 2, 27,28 sin embargo, otros reportan que esta diferencia no es un factor contribuyente en el desarrollo de la enfermedad, por lo que esta inconsistencia puede sugerir la necesidad de más estudios que puedan dilucidar su utilidad o no.…”

“…30 Por otro lado, en el caso de pacientes con Diabetes Mellitus tipo 2, el aumento más notorio y crónico de Bacteroides, Prevotella y Xylanibacter, conllevan a procesos de baja inflamación crónica y formación de ácidos grasos a partir de acetato que explican en parte la resistencia progresiva a receptores de insulina, además de relacionarse con producción de citoquinas proinflamatorias que pueden predisponer efectos de angiogénesis, daño endotelial y afección micro y macrovascular especialmente asociada con IL-12. 30,31 El uso de probióticos que contengan Lactobacillus acidophilus y Bifidobacterium lactis ha demostrado favorecer su concentración en la microbiota intestinal, lo que se traduce en disminución de la glicemia en diabéticos tipo 2, sin embargo, esto parece ser controversial según otros autores, la evidencia actual no recomienda su uso terapéutico a pesar de tener bases teóricas que lo sustente 26,28,30 . Por otro lado, el trasplante de microbiota intestinal ha demostrado aumentar la sensibilidad de receptores a la insulina por mecanismos no bien esclarecidos y se asocia con aumento de niveles butirato, de esta forma se relacionan a bacterias como F. praunitzii que sean productoras de butirato como elementos que previenen la translocación de endotoxinas y bacterias de la microbiota intestinal y se cataloga como factor protector e insulinosensibilizador.…”

<i>In silico</i> analysis of bacterial metabolism of glutamate and GABA in the gut in a rat model of obesity and type 2 diabetes

“…We previously described a rat model of obesity and diabetes [ 13 ] produced by feeding adult male Wistar rats a high-fat diet (HFD; 22% fat; #821424, SDS, UK) for 12 weeks in combination with an intraperitoneal (I/P) injection of citrate buffer vehicle (pH 4.4; Obese group) or the HFD for 12 weeks in combination with a single dose of streptozotocin (STZ; 30 mg kg-1 injected IP at week 4; Diabetic group). Two control groups were included; both were fed a normal diet (RM1, Rat and Mouse No.…”

“…After 12 weeks, animals were housed in clean cages individually overnight, and faecal pellets were collected. Bacterial genomic DNA was isolated within one day of collection and immediately stored at −80°C as described previously [ 13 ].…”

“…Taxonomic profiles were generated for each group by 16S rRNA gene sequencing, and molecular functions were predicted from them by PICRUSt [ 11 ]; the detailed methodology for the bioinformatic analysis has been described previously [ 13 ]. The SRA accession number for the sequencing data is “SRP152214”.…”